The condensation of homophthalic anhydrides with Schiff bases is being investigated as well as the utility of this reaction in the synthesis of a variety of naturally occurring benzophenanthridine and protoberberine aLkaloids. Specific objectives within these classes have been selected in view of demonstrated antileukemic activities. We are also investigating the binding of these alkaloids to DNA, their rate of addition to thiols, their in vitro cytotoxicities, and their in vivo antileukemic activities. We hope to develop a versatile approach to the synthesis of these alkaloids which will allow production of a wide-range of related compounds of value in the investigation of pharmacological structure-activity relationships using natural product templates.